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Background In low-gradient severe aortic stenosis (AS), reduced left ventricular ejection fraction (LVEF <50%) is practically used to define low flow and prompt dobutamine stress echocardiography to discern pseudo-severe AS. In patients with preserved LVEF, stroke volume index (SVI) <35 mL/m² is typically used. However, both are volume-based surrogates. Transaortic flow rate (TAFR), calculated as stroke volume divided by left ventricular ejection time, may better reflect true flow. Nonetheless, comparative data between TAFR and established metrics remain limited. We aimed to evaluate the prognostic value of TAFR in symptomatic low-gradient severe AS. Methods We retrospectively identified patients with low-gradient severe AS (AVA ≤1 cm 2 and peak velocity (Vmax) <4 m/s or mean gradient (MG) <40 mm Hg) who underwent transcatheter aortic valve replacement at Mayo Clinic sites (2017–2023). The primary outcome was 1-year all-cause mortality. Survival was assessed using Kaplan-Meier and Cox proportional hazards models. Results Among 475 patients included (mean age 85±8 years; 49% women), 242 (51%) had TAFR <220 mL/s, 165 (35%) had EF <50%, and 221 (47%) had SVI <35 mL/m 2 . Low TAFR was significantly associated with higher 1-year mortality even after stratifying by EF or SVI. In multivariate analysis, TAFR was an independent predictor of mortality (HR 2.38; 95% CI 1.19 to 4.76, p=0.014) after adjusting for reduced LVEF, low SVI, gender, chronic kidney disease and mitral and tricuspid regurgitation. Conclusions In patients with symptomatic low-gradient severe AS, low TAFR, not SVI or LVEF, is independently associated with mortality and may offer more accurate measure of flow state for clinical staging.

Abstract A short diagnosis-to-treatment interval independently predicts inferior outcomes in follicular lymphoma. Using international discovery and validation cohorts, we demonstrate its prognostic value beyond established prognostic indices, with implications for risk stratification, clinical trial design, and interpretation.

Abstract Hairy cell leukemia (HCL) and HCL variant (HCLv) are distinct, rare, and chronic splenic B-cell lymphomas/leukemias that partially overlap in clinicopathologic presentation but differ in genetic basis, prognosis, and management. HCL is caused by the BRAF-V600E kinase–activating mutation in &gt;95% of the patients, usually has excellent responses to chemotherapy with purine analogues, and is also amenable to BRAF inhibitor–based targeted treatments. In contrast, HCLv lacks BRAFV600E mutation, requires combined therapy with purine analogues in addition to rituximab, and generally shows less durable responses. Here, an international team of hematologists, experts on these rare diseases, was convened by the Hairy Cell Leukemia Foundation to update the previous guidelines (published in 2017) by providing a summary of current methods to diagnose and manage patients with HCL and HCLv as well as a prospective on newer targeted therapies to further improve outcomes.

Abstract We evaluated outcomes by management type for patients with stage IA nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) in the Global NLPHL One Working Group retrospective database of 2243 patients with stages I to IV disease diagnosed from 1992 to 2021 at 38 international institutions. A total of 779 patients had stage IA disease with median age of 35 years (range, 3-89) and median follow-up of 6.1 years. The 6-year progression-free survival (PFS) and overall survival were 86.3% and 97.7%, respectively. Outcomes were analyzed for the 2 groups: complete resection and unresected disease. Patients with a complete resection and observation alone (n = 99) had a 6-year PFS of 65.5% vs 90.5% for those who received radiotherapy (RT) (n = 53). Patients with unresected disease (n = 627; 80.5%) had a 6-year PFS of 62.0% for rituximab alone (n = 31), 89.6% for RT alone (n = 325), 76.8% for ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) alone (n = 40), and 94.3% for ABVD plus RT (n = 130). A total of 127 patients relapsed (16.3%), of which 25 (19.7%) had transformation. Our analysis suggests the following: (1) RT improves the PFS in patients with completely resected disease; (2) rituximab or ABVD alone does not appear to achieve a durable response; and (3) chemotherapy was not observed to add additional PFS benefit when used in combination with RT. Thus, for stage IA NLPHL, RT alone is likely sufficient for definitive treatment.

Abstract Background Repotrectinib, a next-generation ROS1/TRK tyrosine kinase inhibitor, is approved for ROS1 fusion-positive non-small cell lung cancer and NTRK fusion-positive solid tumors. Its side effects and safety management strategies require further characterization. Patients and Methods The safety profile of repotrectinib (treatment-emergent/related adverse events [TEAEs/TRAEs]) was established in patients who initiated treatment at the recommended dose (160 mg daily [QD] for 14 days, then 160 mg twice daily [BID]) across all cohorts of the global, multicenter phase 1/2 TRIDENT-1 study. AE management strategies were outlined. Results In 472 patients, the most common TRAEs (dizziness [58%] and dysgeusia [50%]) were likely TRK inhibition-related. Median relative dose intensity was 90%; 14% (n = 66/472) of patients did not increase their initial QD dose to BID (mostly due to CNS AEs). Rates of dizziness (median onset, 7 days) were similar in patients with/without baseline brain metastases. Dose modifications downgraded severity or resolved dizziness in 78% of patients; 58% of patients had pharmacologic intervention without dose modification. Dizziness was downgraded/resolved in 62% (n = 120/195) of patients who did not receive dose modification or pharmacologic intervention. Treatment-related cognitive impairment and weight gain occurred in 19% and 12% of patients, respectively. Treatment-emergent withdrawal pain occurred in 14% of patients (median resolution time, 2.1 weeks). Dose interruption and reduction from TRAEs occurred in 39% and 38% of patients, respectively; 10% reported later re-escalation back to 160 mg BID. Conclusion Many repotrectinib AEs, including neurological AEs secondary to TRK inhibition, were mitigated with appropriate management, including dose modification and/or pharmacologic intervention.

ABSTRACT Background and Aims Primary sclerosing cholangitis (PSC) is a progressive cholestatic liver disease with a high risk of malignancy and limited therapeutic options. Both the American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver (EASL) recommend structured baseline evaluation, fibrosis staging and longitudinal surveillance. However, real‐world adherence to these practices in North America remains unclear. Methods We conducted a retrospective cohort study of 1300 patients with PSC enrolled in the Consortium for Autoimmune Liver Diseases (CALiD) registry between 2018 and 2024 across 19 centres in North America. Guideline adherence was assessed for diagnostic measures at baseline (colonoscopy to establish IBD status and noninvasive fibrosis staging) and longitudinal surveillance (colonoscopy in PSC‐IBD, abdominal imaging for hepatobiliary cancer surveillance and CA 19‐9 testing). Prescribing patterns for ursodeoxycholic acid (UDCA) were also characterised. Multivariable logistic regression was used to evaluate demographic, clinical and socioeconomic predictors of adherence. Results At diagnosis, 78.8% of eligible patients with available data underwent colonoscopy to establish IBD status, and 45% underwent noninvasive fibrosis staging. During follow‐up, only 30%–35% of patients with PSC‐IBD underwent colonoscopy annually, while abdominal imaging for hepatobiliary cancer surveillance declined from 74% at Year 1 to 51% by Year 4. CA 19‐9 testing was documented in 47% over 5‐year period. UDCA was prescribed in 51% at baseline, with median dose of 12.5 mg/kg/day. Socioeconomic factors, including lower education and household income, were associated with reduced adherence, while cirrhosis strongly predicted completion of surveillance imaging. Conclusions Adherence to guideline‐based care in PSC remains suboptimal in North America Suboptimal adherence was observed for strongly recommended practices with longstanding guideline support (colonoscopy to establish IBD status; annual CRC surveillance in PSC‐IBD) as well as practices where guideline consensus has evolved more recently or where societies differ (baseline fibrosis assessment; hepatobiliary cancer imaging). Efforts to standardise care and address socioeconomic barriers are urgently needed to improve outcomes.

BACKGROUND: Burnout remains prevalent among anesthesiology residents. Contributing workplace factors include limited control over scheduling, unpredictable hours, critical patient care needs, and other residency challenges. The Family Anesthesia Experience (FAX) is a program designed to educate residents and their support persons on wellness and residency demands. The focus of this multisite study was to evaluate the impact of FAX on first year clinical anesthesiology (CA1, ie, PGY2s) residents’ wellness. METHODS: This was a prospective evaluation study involving 15 US anesthesiology residency programs, 13 of which completed FAX. CA1 wellness was evaluated through surveys assessing perceived stress as the primary outcome, with exploratory outcomes including burnout, depression, psychological wellness, and social support. Additionally, changes in support persons’ understanding and knowledge of residency demands were tracked over time. The study included a historical control group of 302 CA1s (2019-2021) who did not participate in FAX, and an intervention group of 88 CA1s that participated in FAX (2021-2022). Statistical analyses compared changes in metrics between groups using linear mixed models and generalized linear models. RESULTS: Significant reductions in perceived stress were observed in the intervention group at 6 months post-FAX (mean change = –2.14, 95% CI, –3.95 to –0.34; P = .021, effect size = 0.58) relative to the control group, but there was no sustained difference at 12 months. Compared to the control support persons, intervention support persons reported increased understanding of residency demands, with significant improvements at 6 (mean change = 2.80, 95% CI, 1.12–4.48; P = .001, effect size = 0.77) and 12 (mean change = 2.59, 95% CI, 0.12–5.05; P = .039, effect size = 0.71) months. Improvement in support persons’ understanding did not predict changes in CA1 wellness outcomes. First generation physician residents reported lower family support at baseline but showed significant improvements in family support at 6 months (mean change = 3.05 points; 95% CI, 0.25–5.84; P = .033; effect size = 1.23) compared to their non first generation peers. CONCLUSIONS: FAX participation was associated with reduced perceived stress in residents up to 6 months post-intervention. First generation physicians experienced greater improvements in perceived family support compared to their non first generation peers. Our findings suggest that resident wellness may be enhanced by engaging both residents and their support persons in an educational wellness program that outlines the professional expectations and demands of anesthesiology residency training.